Respiratory mucosal immunization with adenovirus gene transfer vector induces helper CD4 T cell-independent protective immunity
✍ Scribed by Jingyu Mu; Mangalakumari Jeyanathan; Christopher R. Shaler; Carly Horvath; Daniela Damjanovic; Anna Zganiacz; Kapilan Kugathasan; Sarah McCormick; Zhou Xing
- Book ID
- 102340745
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 434 KB
- Volume
- 12
- Category
- Article
- ISSN
- 1099-498X
- DOI
- 10.1002/jgm.1487
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✦ Synopsis
Abstract
Background
Virus‐vectored vaccine is a powerful activator of CD8 T cell‐mediated immunity and is especially amenable to respiratory mucosal immunization, offering hopes for use in humans with diminished helper CD4 T cell function. However, whether virus‐mediated mucosal immunization can produce immune protective CD8 T cells without the CD4 T cell help remains to be investigated.
Methods
We used a replication‐deficient adenovirus vector expressing an Mycobacterium tuberculosis antigen Ag85A for intranasal vaccination and evaluated its effect on CD8 T cell activation and protection in mice depleted of CD4 T cells.
Results
Intranasal vaccination of CD4 T cell‐depleted mice led to suboptimal generation of Ag‐specific tetramer^+^ or interferon (IFN)‐γ‐producing CD8 T cells in the lung and spleen but this was observed mainly at the early time after vaccination. Reduced CD8 T cell priming was also accompanied by decreased CD8 T cell responses (CTL). Nevertheless, the ratio of Ag‐specific CD8 T cells to IFN‐γ‐producing CD8 T cells in CD4 T cell‐depleted hosts remained comparable to that in CD4 T cell‐competent hosts. Furthermore, the ‘unhelped’ CD8 T cells also displayed a similar immune phenotype as the ‘helped’ counterparts. The animals with ‘unhelped’ CD8 T cells were as well‐protected from pulmonary M. tuberculosis challenge as those with ‘helped’ CD8 T cells in the absence of CD4 T cells.
Conclusions
The data obtained in the present study suggest that the fully immune protective CD8 T cells can still be generated by respiratory mucosal viral‐mediated immunization without CD4 T cells and that CD8 T cells, ‘helped’ or ‘unhelped’, can confer significant protection against pulmonary tuberculosis independent of CD4 T cells. Copyright © 2010 John Wiley & Sons, Ltd.